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PubMed1981

Secondary vestibulocerebellar projections to flocculonodular lobe in a prosimian primate, Galago senegalensis.

The organization of vestibulocerebellar projections to the flocculonodular and adjacent cortices were studied in Galago using horseradish peroxidase (HRP). Implants of HRP pellets or injections (0.14-0.95 microliter) were placed in floccular, parafloccular, nodular, and uvular cortices. Following survival times of 18-25 hours animals were killed via transcardiac perfusion of heparinized saline followed by a buffered solution of paraformaldehyde and glutaraldehyde. Tissues were processed using DAB as the chromogen. Consequent to floccular implants HRP-positive cells are found bilaterally in medial (MVN), spinal (SpVN), and superior (SVN) vestibular nuclei. Labeled neurons are present in the ipsilateral subgroup y and interstitial nucleus of the eighth nerve. The prepositus hypoglossal nuclei also contained HRP-positive somata. A column of labeled cells is present exclusively in dorsomedial MVN subsequent to injection of the paraflocculus. Injections of nodular cortex reveal a distinct bilateral projection to this cortical area. Many labeled cells are located in SpVN, MVN, SVN, subgroups x and y, the interstitial nucleus, and the ganglion of the eighth nerve. Labeled somata are concentrated in dorsal and dorsolateral SpVN and in a bandlike configuration in subgroup x. HRP-reactive cells appear to have a differential rostrocaudal distribution in MVN, while the majority of positive cells in SVN are found in central portions of the nucleus. After HRP injection into the transition area between nodular and uvular cortices, labeled neurons are present in MVN, SpVN, and the prepositus hypoglossal nucleus. A similar distribution of HRP-positive cells is seen following injections of ventral uvula; however, cells are markedly fewer in number. In no case, subsequent to injection of the flocculonodular lobe and adjacent cortices, are HRP-labeled neurons found in the lateral vestibular nucleus.

Animals↗
PubMed1999

Control of spatial orientation of the angular vestibulo-ocular reflex by the nodulus and uvula of the vestibulocerebellum.

Eye velocity produced by the angular vestibulo-ocular reflex (aVOR) tends to align with the summed vector of gravity and other linear accelerations [gravito-inertial acceleration (GIA)]. Defined as "spatial orientation of the aVOR," we propose that it is controlled by the nodulus and uvula of the vestibulocerebellum. Here, electrical stimulation, injections of the GABAA agonist, muscimol, and single-cell recordings were utilized to investigate this spatial orientation. Stimulation, injection, and recording sites in the nodulus were determined in vivo by MRI and verified in histological sections. MRI proved to be a sensitive, reliable way to localize electrode placements. Electrical stimulation at sites in the nodulus and sublobule d of the uvula produced nystagmus whose slow-phase eye-velocity vectors were either head centric or spatially invariant. When head centric, the eye velocity vector remained within +/- 45 degrees of the vector obtained with the animal upright, regardless of head position with respect to gravity. When spatially oriented, the vector remained relatively constant in space in one on-side position, with respect to the vector determined with the animal upright. A majority of induced movements from the nodulus were spatially oriented. Spatially oriented movements were generally followed by after-nystagmus, which had the characteristics of optokinetic after-nystagmus (OKAN), including orientation to the GIA. After muscimol injections, horizontal-to-vertical cross-coupling was lost or reduced during OKAN in tilted positions. This supports the hypothesis that the nodulus mediates yaw-to-vertical or roll cross-coupling. The injections also shortened the yaw-axis time constant and produced contralateral horizontal spontaneous nystagmus, whose velocity varied as a function of head position with regard to gravity. Nodulus units were tested with static head tilt, sinusoidal oscillation around a spatial horizontal axis with the head in different orientations relative to the pitching plane, and off-vertical axis rotation (OVAR). The direction of the response vectors of the otolith-recipient units in the nodulus, determined from static and/or dynamic head tilts, were confirmed by OVAR. These vector directions lay close to the planes of the vertical canals in 7/10 units; many units also had convergent input from the vertical canals. It is postulated that the orientation properties of the aVOR result from a transfer of otolith input regarding head tilt along canal planes to canal-related zones of the nodulus. In turn, Purkinje cells in these zones project to vestibular nuclei neurons to control eye velocity around axes normal to these same canal planes.

Animals↗
PubMed1975

Unit activity in vestibular nucleus of the alert monkey during horizontal angular acceleration and eye movement.

Single units were recorded from the vestibular nuclei of unanesthetized monkeys that were rotated in the horizontal plane while simultaneously pressing individual buttons in a controlled array which turned with hem. Using this behavioral paradigm, it was possible to 1) determine the relationship of unit discharge to eye movements measured by the DC-coupled electrooculogram and calibrated by the button-press task, and 2) determine the relationship of unit discharge to horizontal acceleration, either with or without the compensatory eye movements evoked by vestibular stimulation. Based on their responses during vestibular stimulation and/or eye movements, neurons in the vestibular nuclei (77% of our sample was in the medial nucleus) could be divided into four groups...

Acceleration↗
PubMed2001

Differential induction of brain-derived neurotrophic factor mRNA in rat inferior olive subregions following unilateral labyrinthectomy.

Vestibular compensation, the neuronal process underlying behavioral recovery from vestibular dysfunction produced by unilateral labyrinthectomy, is attributed to functional reorganization of neuronal circuits in the brainstem and cerebellum. Climbing fibers originating from the inferior olive are suggested to play a crucial role in this compensatory process. To assess the possible contribution of brain-derived neurotrophic factor (BDNF) to the function of climbing fibers during vestibular compensation, we investigated the BDNF mRNA expression in the rat inferior olive after unilateral labyrinthectomy by quantitative in situ hybridization. We found several induction patterns depending on the subregions of the inferior olive 6 h after unilateral labyrinthectomy. First, in the dorsal cap and the ventrolateral outgrowth, the expression levels increased on the side contralateral to the lesion and decreased on the ipsilateral side. Second, in the beta nucleus, C subnucleus of the medial accessory olive, and A/B subnuclei of the medial accessory olive, we detected an increase in the mRNA expression level on the side contralateral to the lesion, but no changes in the expression level on the ipsilateral side. In the beta nucleus, where the strongest induction was observed, the mRNA expression level increased nearly five-fold. Third, in the dorsomedial cell column, the mRNA expression levels increased on both sides. Finally, we did not detect significant changes in mRNA expression levels in the other subregions of the inferior olive, the dorsal accessory olive, principal olive and rostral medial accessory olive. The changes in BDNF mRNA expression reverted to control levels by 72 h after the labyrinthectomy. The inferior olive subregions that showed changes in BDNF mRNA expression levels send climbing fibers to the cerebellar cortical regions that, in turn, project to the vestibular nuclei. Therefore, BDNF induced in these subregions could contribute to the functional reorganization of the olivo-cerebellar system for vestibular control.

Animals↗
PubMed1996

Pattern of selected calcium-binding proteins in the vestibular nuclear complex of two rodent species.

The distribution of immunoreactivity to calbindin, calretinin, and parvalbumin in the vestibular nuclear complex and the adjacent nucleus prepositus hypoglossi was studied in rats and gerbils. The distribution of stained fibers was the same for both rodent species. All three calcium-binding proteins were present in vestibular afferents. However, none of the three proteins were present in all afferent fibers. Many fibers were labeled in the vestibular nerve and in fascicles of the descending vestibular nucleus, as well as ascending fibers in the superior vestibular nucleus and fibers directed to the medial vestibular nucleus. Labeled terminals were present in the medial vestibular nucleus, especially along the ventricular border, in the neuropil of the superior vestibular nucleus, and scattered in the descending and ventral portions of the lateral vestibular nucleus. Calbindin- and parvalbumin-positive terminals, but not calretinin-positive terminals, were present in the neuropil of the dorsal lateral vestibular nucleus, especially surrounding the large neuronal somas. Some of these terminals are presumably from cerebellar Purkinje cells, which were also labeled by both antibodies. The pattern of parvalbumin immunoreactivity was slightly different from that of calbindin, indicating that parvalbumin might be contained in additional fibers. Some neurons in the vestibular nuclear complex were labeled with antibodies to calretinin, but few cells were stained with either calbindin or parvalbumin antibodies. The largest group of calretinin-positive cells was a cluster of small- to medium-sized neurons located in a densely stained mesh of dendrites and terminals in the medial vestibular nucleus, adjacent to the ventricular border.

Animals↗
PubMed1997

NaG: a sodium channel-like mRNA shared by Schwann cells and other neural crest derivatives.

NaG, a member of subfamily 2, was originally characterized as a "glial" sodium channel, and is expressed at high levels in Schwann cells in vivo. However, NaG has also been shown by in situ hybridization to be highly expressed in rat dorsal root ganglion (DRG) neurons, which, like Schwann cells, are neural crest derivatives. In the present study, we used non-isotopic in situ hybridization with a riboprobe for NaG, in conjunction with RT-PCR, to determine whether NaG is expressed in tissues related to the DRG either by neural crest origin or sensory function. We found that the expression of significant levels of NaG mRNA was restricted to derivatives of the neural crest (neurons of DRG, trigeminal ganglion and mesencephalic nucleus of the trigeminal nerve, and Schwann and satellite cells); the absence of NaG from superior cervical ganglion neurons and adrenal medulla chromaffin cells indicates that not all neural crest derived neural elements express NaG. NaG was not observed in sensory neurons (retina, vestibular ganglion, spiral ganglion, olfactory epithelium) that are not of neural crest origin. Our results indicate that NaG mRNA is expressed not only in Schwann cells, but also in a spectrum of neuronal cell types with afferent function of neural crest origin. NaG thus appears to represent a transcript encoding a sodium channel or sodium channel-like protein that is uniquely expressed by both Schwann cells and afferent neurons of neural crest origin.

Animals↗
PubMed2000

Discharge characteristics of axotomized abducens internuclear neurons in the adult cat.

The aim of the present work was to characterize the axotomy-induced changes in the discharge properties of central nervous system neurons recorded in the alert behaving animal. The abducens internuclear neurons of the adult cat were the chosen model. The axons of these neurons course through the contralateral medial longitudinal fascicle and contact the medial rectus motoneurons of the oculomotor nucleus. Axotomy was carried out by the unilateral transection of this fascicle (right side) and produced immediate oculomotor deficits, mainly the incapacity of the right eye to adduct across the midline. Extracellular single-unit recording of abducens neurons was carried out simultaneously with eye movements. The main alteration observed in the firing of these axotomized neurons was the overall decrease in firing rate. During eye fixations, the tonic signal was reduced, and, on occasion, a progressive decay in firing rate was observed. On-directed saccades were not accompanied by the high-frequency spike burst typical of controls; instead, there was a moderate increase in firing. Similarly, during the vestibular nystagmus, neurons hardly modulated during both the slow and the fast phases. Linear regression analysis between firing rate and eye movement parameters showed a significant reduction in eye position and velocity sensitivities with respect to controls, during both spontaneous and vestibularly induced eye movements. These firing alterations were observed during the 3 month period of study after lesion, with no sign of recovery. Conversely, abducens motoneurons showed no significant alteration in their firing pattern. Therefore, axotomy produced long-lasting changes in the discharge characteristics of abducens internuclear neurons that presumably reflected the loss of afferent oculomotor signals. These alterations might be due to the absence of trophic influences derived from the target.

Abducens Nerve↗
PubMed1993

Distribution of calcitonin gene-related peptide mRNA and immunoreactivity in the rat central and peripheral vestibular system.

The distribution of calcitonin gene-related peptide (CGRP) mRNA and immunoreactivity (CGRPi) was examined in sections of brainstem and decalcified temporal bones to study the peptidergic innervation patterns in both the central and peripheral vestibular system. In the brainstem, neuron somata associated with the vestibular system and containing CGRP mRNA and CGRPi were found in both the dorsolateral and medial regions of the group E vestibular efferents as well as scattered throughout the caudal pontine reticular nucleus (CPR). The only labelled neuron somata containing CGRP mRNA and CGRPi in the temporal bone were found in the gustatory geniculate ganglion. Coarse CGRPi axons were traced ventrally from the dorsolateral and medial group E somata and dorsally from the CPR somata. CGRPi axons from the medial group E and CPR crossed the facial nerve ventral to the facial genu before entering the eighth nerve root. Immunoreactive axons projected from medial group E cells, beneath the ependyma of the fourth ventricle, to the contralateral brainstem. Unmyelinated CGRPi fibers passed among the primary afferent fibers in Scarpa's ganglion and continued through the subepithelial regions of the vestibular end-organs. Within the neurosensory epithelia of the maculae and cristae, the CGRPi axons ramified to produce numerous CGRPi terminals. An efferent neuromodulatory role of CGRP in the vestibular system is inferred from the wide distribution of CGRP mRNA and immunoreactivity found within efferent vestibular neurons.

Animals↗
PubMed1993

Direct projection from the nucleus of the optic tract to the medial vestibular nucleus in the cat.

The nucleus of the optic tract (NOT) serves as an important visuo-motor relay between the retina and preoculomotor structures that mediate optokinetic nystagmus. In the present study, the efferent targets of NOT were investigated using biocytin as an anterograde tracer. Following biocytin injections into NOT, labeled fibers were observed in each of the following efferent pathways: (1) those that project to the contralateral NOT via the posterior commissure; (2) those that course through the nucleus reticularis pontis oralis to terminate in the nucleus reticularis tegmenti pontis; and (3) those that descend via the medial lemniscus to the level of the medulla to terminate in the dorsolateral pontine nucleus, nucleus prepositus hypoglossi, medial vestibular nucleus and the inferior olive. Direct projections from the NOT to the medial vestibular nucleus may contribute to the residual optokinetic responses of the vestibular nucleus neurons following cerebellar or inferior olivary lesions.

Animals↗
PubMed1992

Detection of rotating gravity signals.

It is shown in the preceding paper that neurons with two-dimensional spatio-temporal properties to linear acceleration behave like one-dimensional rate sensors: they encode the component of angular velocity (associated with a rotating linear acceleration vector) that is normal to their response plane. During off-vertical axis rotation (OVAR) otolith-sensitive neurons are activated by the gravity vector as it rotates relative to the head. Unlike "one-dimensional" linear accelerometer neurons which exhibit equal response magnitudes for both directions of rotation, "two-dimensional" neurons can be shown to respond with unequal magnitudes to clockwise and counterclockwise off-vertical axis rotations. The magnitudes of the sinusoidal responses of these neurons is not only directionally selective but also proportional to rotational velocity. Thus, responses from such "two-dimensional" neurons may represent the first step in the computations necessary to generate the steady-state eye velocity during OVAR. An additional step involving a nonlinear operation is necessary to transform the sinusoidally modulated output of these neurons into a signal proportional to sustained eye velocity. Similarly to models of motion detection in the visual system, this transformation is proposed to be achieved through neuronal operations involving mathematical multiplication followed by a leaky integration by the velocity storage mechanism. The proposed model for the generation of maintained eye velocity during OVAR is based on anatomical and physiological properties of vestibular nuclei neurons and capable of predicting the experimentally observed steady-state characteristics of the eye velocity.

Acceleration↗
PubMed2001

Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons.

The POU domain transcription factors Brn3a, Brn3b and Brn3c are required for the proper development of sensory ganglia, retinal ganglion cells, and inner ear hair cells, respectively. We have investigated the roles of Brn3a in neuronal differentiation and target innervation in the facial-stato-acoustic ganglion. We show that absence of Brn3a results in a substantial reduction in neuronal size, abnormal neuronal migration and downregulation of gene expression, including that of the neurotrophin receptor TrkC, parvalbumin and Brn3b. Selective loss of TrkC neurons in the spiral ganglion of Brn3a(-/-) cochlea leads to an innervation defect similar to that of TrkC(-/-) mice. Most remarkably, our results uncover a novel role for Brn3a in regulating axon pathfinding and target field innervation by spiral and vestibular ganglion neurons. Loss of Brn3a results in severe retardation in development of the axon projections to the cochlea and the posterior vertical canal as early as E13.5. In addition, efferent axons that use the afferent fibers as a scaffold during pathfinding also show severe misrouting. Interestingly, despite the well-established roles of ephrins and EphB receptors in axon pathfinding, expression of these molecules does not appear to be affected in Brn3a(-/-) mice. Thus, Brn3a must control additional downstream genes that are required for axon pathfinding.

Animals↗
PubMed2003

Central projections of the saccular and utricular nerves in macaques.

The central projections of the utricular and saccular nerve in macaques were examined using transganglionic labeling of vestibular afferent neurons. In these experiments, biotinylated dextran amine was injected directly into the saccular or utricular neuroepithelium of fascicularis (Macaca fascicularis) or rhesus (Macaca mulatta) monkeys. Two to 5 weeks later, the animals were killed and the peripheral vestibular sensory organs, brainstem, and cerebellum were collected for analysis. The principal brainstem areas of saccular nerve termination were lateral, particularly the spinal vestibular nucleus, the lateral portion of the superior vestibular nucleus, ventral nucleus y, the external cuneate nucleus, and cell group l. The principal cerebellar projection was to the uvula with a less dense projection to the nodulus. Principle brainstem areas of termination of the utricular nerve were the lateral/dorsal medial vestibular nucleus, ventral and lateral portions of the superior vestibular nucleus, and rostral portion of the spinal vestibular nucleus. In the cerebellum, a strong projection was observed to the nodulus and weak projections were present in the flocculus, ventral paraflocculus, bilateral fastigial nuclei, and uvula. Although there is extensive overlap of saccular and utricular projections, saccular inputs to the lateral portions of the vestibular nuclear complex suggest that saccular afferents contribute to the vestibulospinal system. In contrast, the utricular nerve projects more rostrally into areas of known concentration of vestibulo-ocular related cells. Although sparse, the projections of the utricle to the flocculus/ventral paraflocculus suggest a potential convergence with floccular projection inputs from the vestibular brainstem that have been implicated in vestibulo-ocular motor learning.

Afferent Pathways↗
PubMed2005

Independent effects of simultaneous inputs from the saccule and lateral semicircular canal. Evaluation using VEMPs.

OBJECTIVE: To determine the effects of stimulation of bilateral lateral semicircular canals (LSCCs) by accelerated rotation and caloric stimulation of unilateral LSCC on vestibular evoked myogenic potentials (VEMPs) in healthy volunteers. METHODS: In experiment 1, VEMPs were recorded while subjects (n = 11) were seated in a rotational chair and angular acceleration around the earth-vertical axis was provided. Amplitudes of p13-n23 were corrected using background muscle activities. In experiment 2, subjects (n = 8) in the semilateral position kept the LSCC in the vertical position and activated the sternocleidomastoid muscle by twisting the neck. After irrigating the external auditory canal with ice water, VEMPs were recorded on the irrigated side. In experiment 3, the same setting as experiment 2 was applied (n = 6), and hot water of 44 degrees C was used for irrigation. RESULTS: There were no significant differences in latencies of p13 or n23, and in corrected amplitudes by either rotatory or caloric stimulation. CONCLUSIONS: Simultaneous stimulation of LSCCs has little effect on VEMPs. SIGNIFICANCE: No functional interaction between the saccule and LSCC was detected in VEMPs, although convergence of semicircular canal and otolith nerve inputs onto single vestibular nucleus neurons has been demonstrated electrophysiologically in animal experiments.

Adult↗
PubMed1990

Evidence that NMDA receptors contribute to synaptic function in the guinea pig medial vestibular nucleus.

Single medial vestibular nucleus neurons were recorded from guinea pig brainstem slices in vitro while superfusing with the selective N-methyl-D-aspartate (NMDA) antagonists, MK801 and CPP. The majority of neurons tested showed a decrease in firing rate in response to these NMDA antagonists, suggesting that NMDA receptors may contribute to the resting activity of MVN neurons.

Action Potentials↗
PubMed1993

Medial vestibular nucleus in the guinea-pig: histaminergic receptors. I. An in vitro study.

Antihistaminergic drugs are currently used for the symptomatic treatment of vestibular-related syndromes such as vertigo and motion sickness. We therefore investigated whether histamine could modulate the firing of medial vestibular nuclei neurons (MVNn). Recently, we have demonstrated that different cell types are present among MVNn in guinea-pig brainstem slices. Bath-application of histamine at 10(-4) or 10(-5) M induced a small membrane depolarization accompanied by a slight decrease in membrane resistance and a reversible increase in spontaneous firing in all MVN cell types. These effects were presumably postsynaptic as they persisted in a low-calcium/high-magnesium solution. Using a variety of agonists and antagonists of histamine receptors (H1, H2 and H3), we conclude that these effects are mediated by H2 receptors. The companion paper is concerned with an in vivo study of the histaminergic modulation of the vestibular function (Yabe et al., in press).

Animals↗
PubMed2005

The effects of vestibular system lesions on autonomic regulation: observations, mechanisms, and clinical implications.

The loss of labyrinthine inputs in patients or animal models has been demonstrated to affect autonomic regulation. Considerable evidence suggests that vestibular-autonomic responses serve to adjust blood pressure and respiratory activity during movement and postural alterations. However, following peripheral vestibular lesions, compensation rapidly occurs, such that autonomic disturbances are not readily evident in patients with chronic labyrinthine dysfunction. This manuscript summarizes the evidence suggesting that vestibular inputs influence autonomic regulation, but that cardiovascular and respiratory responses linked to movement recover quickly subsequent to the loss of labyrinthine signals. In addition, the clinical implications of dysfunction of vestibulo-autonomic reflexes are described. Furthermore, the mechanisms potentially responsible for the return of the ability to produce posturally-related adjustments in blood pressure and respiration following vestibular lesions are discussed. In particular, evidence that somatosensory signals can replace labyrinthine inputs to vestibular nucleus neurons that participate in autonomic regulation is provided.

Animals↗